Fig. 1

Trametinib inhibits MEK1/2 without marked cytotoxicity or apoptosis induction in vitro. A Maximum observed viability reduction (Effect_max in %; 100 % corresponds to a complete loss of cell culture viability) and concentration at which half-maximal effective inhibition is observed (EC₅₀ in nM) in BRAF^mut and BRAF WT melanoma cells were calculated from cell viability data (MUH assay) after 72 hours of treatment with increasing concentrations of trametinib (up to 2 µM). Signals were normalized to the untreated controls. Trametinib EC₅₀ values were calculated in GraphPad Prism. Dashed lines represent the mean values of all data points. B Cropped immunoblots of MAPK pathway activity (phospho-ERK1/2^{Thr202/Tyr204} and phospho-MEK1/2^Ser217/221) in the BRAF WT melanoma cell lines SKMEL23 and SKMEL113 after treatment with trametinib (10 nM) for 6 hours. β-Actin served as the loading control. C Flow cytometric cell cycle analysis of BRAF WT melanoma cells following treatment with trametinib. BRAF WT melanoma cells were treated with trametinib (10 nM) for 24, 48 and 72 hours (mean ± SD, n = 3)